Precursor of Serotonin and Role in Central Fatigue

The central fatigue hypothesis, illustrated in Figure 13.5a, was proposed by Eric Newsholme and colleagues in 198717 as an important mechanism contributing to the development of fatigue during prolonged exercise. This hypothesis predicts that during exercise, free fatty acids (FFAs) are mobilized from adipose tissue and transported via the blood to the muscles to serve as fuel. Because the rate of mobilization is greater than the rate of uptake by the muscle, the blood FFA concentration increases. Both FFAs and the amino acid tryptophan bind to albumin and compete for the same binding sites. Tryptophan is prevented from binding to albumin by the increasing FFA concentration, and therefore, the free tryptophan (fTRP) concentration and the fTRP:BCAA ratio in the blood rise. Furthermore, the plasma concentration of BCAAs falls during prolonged exercise as circulating BCAAs are taken up by the contracting muscles for oxidative metabolism at a higher rate than

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